scholarly journals The Paramount Role of Drosophila melanogaster in the Study of Epigenetics: From Simple Phenotypes to Molecular Dissection and Higher-Order Genome Organization

Insects ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 884
Author(s):  
Jean-Michel Gibert ◽  
Frédérique Peronnet
Keyword(s):  
Drosophila Melanogaster ◽  
Regulation Of Gene Expression ◽  
Higher Order ◽  
Post Translational Modifications ◽  
Histone Marks ◽  
Heterochromatin Formation ◽  
Regulatory Processes ◽  
Chromatin Regulators ◽  
Chromatin Remodeling Complexes

Drosophila melanogaster has played a paramount role in epigenetics, the study of changes in gene function inherited through mitosis or meiosis that are not due to changes in the DNA sequence. By analyzing simple phenotypes, such as the bristle position or cuticle pigmentation, as read-outs of regulatory processes, the identification of mutated genes led to the discovery of major chromatin regulators. These are often conserved in distantly related organisms such as vertebrates or even plants. Many of them deposit, recognize, or erase post-translational modifications on histones (histone marks). Others are members of chromatin remodeling complexes that move, eject, or exchange nucleosomes. We review the role of D. melanogaster research in three epigenetic fields: Heterochromatin formation and maintenance, the repression of transposable elements by piRNAs, and the regulation of gene expression by the antagonistic Polycomb and Trithorax complexes. We then describe how genetic tools available in D. melanogaster allowed to examine the role of histone marks and show that some histone marks are dispensable for gene regulation, whereas others play essential roles. Next, we describe how D. melanogaster has been particularly important in defining chromatin types, higher-order chromatin structures, and their dynamic changes during development. Lastly, we discuss the role of epigenetics in a changing environment.

RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators

2013 ◽  
Vol 450 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Shankha Satpathy ◽  
Arash Nabbi ◽  
Karl Riabowol
Keyword(s):  
Biological Significance ◽  
Type Ii ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Chromatin Regulators ◽  
Cancer Types ◽  
Splicing Isoforms ◽  
Enrichment Techniques ◽  
Affect Cell Growth

The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.

scholarly journals Epigenetic Regulation of Myogenesis: Focus on the Histone Variants

2021 ◽  
Vol 22 (23) ◽  
pp. 12727
Author(s):  
Joana Esteves de Lima ◽  
Frédéric Relaix
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Muscle Development ◽  
Regulation Of Gene Expression ◽  
Histone Variants ◽  
Myoblast Differentiation ◽  
Post Translational Modifications ◽  
Differentiation Status

Skeletal muscle development and regeneration rely on the successive activation of specific transcription factors that engage cellular fate, promote commitment, and drive differentiation. Emerging evidence demonstrates that epigenetic regulation of gene expression is crucial for the maintenance of the cell differentiation status upon division and, therefore, to preserve a specific cellular identity. This depends in part on the regulation of chromatin structure and its level of condensation. Chromatin architecture undergoes remodeling through changes in nucleosome composition, such as alterations in histone post-translational modifications or exchange in the type of histone variants. The mechanisms that link histone post-translational modifications and transcriptional regulation have been extensively evaluated in the context of cell fate and differentiation, whereas histone variants have attracted less attention in the field. In this review, we discuss the studies that have provided insights into the role of histone variants in the regulation of myogenic gene expression, myoblast differentiation, and maintenance of muscle cell identity.

scholarly journals Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression

2018 ◽  
Vol 19 (12) ◽  
pp. 3820 ◽  
Author(s):  
Matteo Spinelli ◽  
Salvatore Fusco ◽  
Claudio Grassi
Keyword(s):  
Gene Expression ◽  
Protein Trafficking ◽  
Regulation Of Gene Expression ◽  
Cysteine Modification ◽  
Post Translational Modifications ◽  
Protein Palmitoylation ◽  
Physiological Phenomenon ◽  
The Impact ◽  
Protein Lipidation

Diet is the main environmental stimulus chronically impinging on the organism throughout the entire life. Nutrients impact cells via a plethora of mechanisms including the regulation of both protein post-translational modifications and gene expression. Palmitoylation is the most-studied protein lipidation, which consists of the attachment of a molecule of palmitic acid to residues of proteins. S-palmitoylation is a reversible cysteine modification finely regulated by palmitoyl-transferases and acyl-thioesterases that is involved in the regulation of protein trafficking and activity. Recently, several studies have demonstrated that diet-dependent molecules such as insulin and fatty acids may affect protein palmitoylation. Here, we examine the role of protein palmitoylation on the regulation of gene expression focusing on the impact of this modification on the activity of chromatin remodeler enzymes, transcription factors, and nuclear proteins. We also discuss how this physiological phenomenon may represent a pivotal mechanism underlying the impact of diet and nutrient-dependent signals on human diseases.

Proteasome activator Blm10 regulates transcription especially during aging

2021 ◽  
Vol 22 ◽  
Author(s):  
Yu-Shan Chen ◽  
Xia Han ◽  
Kui Lin ◽  
Tian-Xia Jiang ◽  
Xiao-Bo Qiu
Keyword(s):  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Histone Marks ◽  
Proteasome Activator ◽  
The Core ◽  
Core Histones ◽  
The Stability

Background: Histones are basic elements of the chromatin, and are critical to controlling chromatin structure and transcription. The proteasome activator PA200 promotes the acetylation-dependent proteasomal degradation of the core histones during spermatogenesis, DNA repair, transcription and cellular aging, and maintains the stability of histone marks. Objective: The study aimed to explore whether the yeast ortholog of PA200, Blm10, promotes degradation of the core histones during transcription and regulates transcription especially during aging. Method: Protein degradation assays were performed to detect the role of Blm10 in histone degradation during transcription. mRNA profiles were compared in WT and mutant BY4741 or MDY510 yeast cells by RNA-sequencing. Results: The core histones can be degraded by the Blm10-proteasome in the non-replicating yeast, suggesting that Blm10 promotes the transcription-coupled degradation of the core histones. Blm10 preferentially regulates transcription in aged yeast, especially transcription of genes related to translation, amino acid metabolism and carbohydrate metabolism. Mutations of Blm10 at F2125/N2126 in its putative acetyl-lysine binding region abolished the Blm10-mediated regulation of gene expression. Conclusion: Blm10 promotes degradation of the core histones during transcription and regulates transcription especially during cellular aging, further supporting the critical role of PA200 in maintaining the stability of histone marks from the evolutionary view. These results should provide meaningful insights into the mechanisms underlying aging and the related diseases.

Small regulatory noncoding RNAs in Drosophila melanogaster: biogenesis and biological functions

2020 ◽  
Vol 19 (4) ◽  
pp. 309-323
Author(s):  
Saeed Soleimani ◽  
Zahra Valizadeh Arshad ◽  
Sharif Moradi ◽  
Ali Ahmadi ◽  
Seyed Javad Davarpanah ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Critical Discussion ◽  
Rnai Pathway ◽  
Biological Functions ◽  
Small Interfering Rnas ◽  
Heterochromatin Formation ◽  
Small Noncoding Rnas ◽  
Small Ncrnas

Abstract RNA interference (RNAi) is an important phenomenon that has diverse genetic regulatory functions at the pre- and posttranscriptional levels. The major trigger for the RNAi pathway is double-stranded RNA (dsRNA). dsRNA is processed to generate various types of major small noncoding RNAs (ncRNAs) that include microRNAs (miRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) in Drosophila melanogaster (D. melanogaster). Functionally, these small ncRNAs play critical roles in virtually all biological systems and developmental pathways. Identification and processing of dsRNAs and activation of RNAi machinery are the three major academic interests that surround RNAi research. Mechanistically, some of the important biological functions of RNAi are achieved through: (i) supporting genomic stability via degradation of foreign viral genomes; (ii) suppressing the movement of transposable elements and, most importantly, (iii) post-transcriptional regulation of gene expression by miRNAs that contribute to regulation of epigenetic modifications such as heterochromatin formation and genome imprinting. Here, we review various routes of small ncRNA biogenesis, as well as different RNAi-mediated pathways in D. melanogaster with a particular focus on signaling pathways. In addition, a critical discussion of the most relevant and latest findings that concern the significant contribution of small ncRNAs to the regulation of D. melanogaster physiology and pathophysiology is presented.

scholarly journals On the role of DNA biomechanics in the regulation of gene expression

2011 ◽  
Vol 8 (65) ◽  
pp. 1673-1681 ◽  
Author(s):  
J. N. Milstein ◽  
J.-C. Meiners
Keyword(s):  
Gene Expression ◽  
Genetic Regulation ◽  
Regulation Of Gene Expression ◽  
Cellular Functions ◽  
Biochemical Processes ◽  
Regulatory Processes ◽  
Linear Sequence ◽  
Cellular Environment ◽  
Cellular Dna

DNA is traditionally seen as a linear sequence of instructions for cellular functions that are expressed through biochemical processes. Cellular DNA, however, is also organized as a complex hierarchical structure with a mosaic of mechanical features, and a growing body of evidence is now emerging to imply that these mechanical features are connected to genetic function. Mechanical tension, for instance, which must be felt by DNA within the heavily constrained and continually fluctuating cellular environment, can affect a number of regulatory processes implicating a role for biomechanics in gene expression complementary to that of biochemical regulation. In this article, we review evidence for such mechanical pathways of genetic regulation.

scholarly journals Heterochromatin-dependent transcription of satellite DNAs in the Drosophila melanogaster female germline

2020 ◽  
Author(s):  
Xiaolu Wei ◽  
Danna G. Eickbush ◽  
Iain Speece ◽  
Amanda M. Larracuente
Keyword(s):  
Drosophila Melanogaster ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Satellite Dnas ◽  
Heterochromatin Formation ◽  
Repeat Units ◽  
Repeated Dnas ◽  
Female Germline ◽  
Insight Into

ABSTRACTLarge blocks of tandemly repeated DNAs—satellite DNAs (satDNAs)—play important roles in heterochromatin formation and chromosome segregation. We know little about how satDNAs are regulated, however their misregulation is associated with genomic instability and human diseases. We use the Drosophila melanogaster germline as a model to study the regulation of satDNA transcription and chromatin. Here we show that complex satDNAs (>100-bp repeat units) are transcribed into long noncoding RNAs and processed into piRNAs (PIWI interacting RNAs). This satDNA piRNA production depends on the Rhino-Deadlock-Cutoff complex and the transcription factor Moonshiner—a previously-described non-canonical pathway that licenses heterochromatin-dependent transcription of dual-strand piRNA clusters. We show that this pathway is important for establishing heterochromatin at satDNAs. Therefore, satDNAs are regulated by piRNAs originating from their own genomic loci. This novel mechanism of satDNA regulation provides insight into the role of piRNA pathways in heterochromatin formation and genome stability.

scholarly journals Fixation of transposable elements in the Drosophila melanogaster genome

2005 ◽  
Vol 85 (3) ◽  
pp. 195-203 ◽  
Author(s):  
XULIO MASIDE ◽  
STAVROULA ASSIMACOPOULOS ◽  
BRIAN CHARLESWORTH
Keyword(s):  
Drosophila Melanogaster ◽  
Transposable Elements ◽  
Genomic Dna ◽  
Molecular Level ◽  
Hybridization Technique ◽  
Small Interfering Rnas ◽  
Heterochromatin Formation ◽  
Large Clusters

We have investigated at the molecular level four cases in which D. melanogaster middle repetitive DNA probes consistently hybridized to a particular band on chromosomes sampled from a D. melanogaster natural population. Two corresponded to true fixations of a roo and a Stalker element, and the others were artefacts of the in situ hybridization technique caused by the presence of genomic DNA flanking the transposable elements (TEs) in the probes. The two fixed elements are located in the β-heterochromatin (20A and 80B, respectively) and are embedded in large clusters of other elements, many of which may also be fixed. We also found evidence that this accumulation is an ongoing process. These results support the hypothesis that TEs accumulate in the non-recombining part of the genome. Their implications for the effects of TEs on determining the chromatin structure of the host genomes are discussed in the light of recent evidence for the role of TE-derived small interfering-RNAs as cis-acting determinants of heterochromatin formation.

O-GlcNAcylation and chromatin remodeling in mammals: an up-to-date overview

2017 ◽  
Vol 45 (2) ◽  
pp. 323-338 ◽  
Author(s):  
Maïté Leturcq ◽  
Tony Lefebvre ◽  
Anne-Sophie Vercoutter-Edouart
Keyword(s):  
Chromatin Remodeling ◽  
Dna Demethylation ◽  
Post Translational Modifications ◽  
Cellular Models ◽  
Active Dna Demethylation ◽  
Chromatin Regulators ◽  
Lysine Specific Demethylase ◽  
The Stability ◽  
Glcnac Transferase

Post-translational modifications of histones and the dynamic DNA methylation cycle are finely regulated by a myriad of chromatin-binding factors and chromatin-modifying enzymes. Epigenetic modifications ensure local changes in the architecture of chromatin, thus controlling in fine the accessibility of the machinery of transcription, replication or DNA repair to the chromatin. Over the past decade, the nutrient-sensor enzyme O-GlcNAc transferase (OGT) has emerged as a modulator of chromatin remodeling. In mammals, OGT acts either directly through dynamic and reversible O-GlcNAcylation of histones and chromatin effectors, or in an indirect manner through its recruitment into chromatin-bound multiprotein complexes. In particular, there is an increasing amount of evidence of a cross-talk between OGT and the DNA dioxygenase ten–eleven translocation proteins that catalyze active DNA demethylation. Conversely, the stability of OGT itself can be controlled by the histone lysine-specific demethylase 2 (LSD2). Finally, a few studies have explored the role of O-GlcNAcase (OGA) in chromatin remodeling. In this review, we summarize the recent findings on the link between OGT, OGA and chromatin regulators in mammalian cellular models, and discuss their relevance in physiological and pathological conditions.

scholarly journals Heterochromatin-dependent transcription of satellite DNAs in the Drosophila melanogaster female germline

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaolu Wei ◽  
Danna G Eickbush ◽  
Iain Speece ◽  
Amanda M Larracuente
Keyword(s):  
Drosophila Melanogaster ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Satellite Dnas ◽  
Heterochromatin Formation ◽  
Repeat Units ◽  
Repeated Dnas ◽  
Female Germline ◽  
Insight Into

Large blocks of tandemly repeated DNAs-satellite DNAs (satDNAs)-play important roles in heterochromatin formation and chromosome segregation. We know little about how satDNAs are regulated, however their misregulation is associated with genomic instability and human diseases. We use the Drosophila melanogaster germline as a model to study the regulation of satDNA transcription and chromatin. Here we show that complex satDNAs (>100-bp repeat units) are transcribed into long noncoding RNAs and processed into piRNAs (PIWI interacting RNAs). This satDNA piRNA production depends on the Rhino-Deadlock-Cutoff complex and the transcription factor Moonshiner—a previously-described non-canonical pathway that licenses heterochromatin-dependent transcription of dual-strand piRNA clusters. We show that this pathway is important for establishing heterochromatin at satDNAs. Therefore, satDNAs are regulated by piRNAs originating from their own genomic loci. This novel mechanism of satDNA regulation provides insight into the role of piRNA pathways in heterochromatin formation and genome stability.

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